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Treadmilling of filaments feeds movement |
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Functions required for movement: |
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Site-directed generation of barbed ends |
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by
N-WASP (resp. ActA)-activated Arp2/3 |
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2) Chemostat maintaining a high steady-state
concentration of ATP-G-actin : Actin, ADF/cofilin, profilin, Capping
protein |
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Movement results from a balance between the
creation of new growing filaments (branching) and death of these filaments
(capping). |
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The velocity of beads depends on the number of
filaments pushing the bead. |
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Movement is controlled by a balance between
filament branching and capping (Carlsson’s model). |
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Velocity is not sensitive to external load
(viscous drag), i.e. the force due to polymerization at the bead surface is
balanced by the internal brake (friction) due to attached filaments. |
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Control of filament turnover |
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Site-directed generation of new filaments: |
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2 mechanisms: |
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Branching Barbed end nucleation (WASP/Arp2/3)
and processive growth |
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(formins) |
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Nucleate actin assembly (FH2 is sufficient) |
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Active as FH2 or FH1-FH2 dimers |
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Bind to barbed ends without greatly affecting
rate parameters for actin assembly and disassembly |
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Postulated to be processive « leaky
cappers » remaining bound to growing barbed ends |
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Formin increases the rate of ATP hydrolysis |
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in
profilin-actin assembly |
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LEBS, CNRS, Gif-sur-Yvette |
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Dominique Pantaloni |
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Marie-France Carlier |
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Emmanuèle Helfer |
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Dominique Didry |
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Diep Lê |
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Stanislav Samarin |
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Sebastian Wiesner |
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Christophe Le Clainche |
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Stéphane
Romero |
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Vincent
Delatour |
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Collaborators |
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(Institut Pasteur) : |
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Coumaran Egile |
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Philippe Sansonetti |
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(Institut Curie): |
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Jacques Prost |
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Cécile Sykes |
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(Harvard
medical school) : |
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Christine Kocks |
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Control of the concentration of soluble proteins
in the motility medium. |
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Control of the surface density of filament
branching enzyme (N-WASP or ActA). |
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Load/velocity relationship: control of the size
of the bead and of the viscosity of the medium. |
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Frequency of filament branching during movement:
two fluorophores (actin and Arp2/3) |
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Biomimetics: Reconstitution of lamellipodium
protrusion (force applied to a membrane, functionalized liposome) |
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Coupling of adhesion and protrusion during cell
migration: concerted actin dynamics at focal contacts and in lamellipodium. |
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Signaling, actin-based motility and
morphogenesis: specifying different motile actin-based structures. |
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Actin filaments have a polar structure |
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They are semi-flexible polymers |
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Assembly dynamics is regulated in vivo |
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Filament assembly is a dissipative reaction
(hydolysis of actin-bound ATP) |
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Control of the [G-actin]/[F-actin] ratio |
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Control of filament turnover |
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Spatial control of the generation of new
filaments (link to signaling) |
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Notizen
